Diseases Commons^™

Identifying And Targeting Cancer Stem Cells In Colorectal Cancer, Amber Harnett

Electronic Thesis and Dissertation Repository

The cancer stem cell hypothesis posits that cancer stem cells (CSCs) are the driving force behind tumour progression and metastasis, making them ideal therapeutic targets. Previous research identified Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a marker of CSCs in colorectal cancer (CRC). However, it is not known whether more than one CSC population exists in CRC. Identifying and targeting CSCs in CRC is important for effective treatment of cancer patients. Here, I show that Keratin-19 (K19) labels intestinal CSCs in mouse tumours that recapitulate the early stages of CRC. Moreover, selective ablation of Lgr5 has no effect on tumour …

Functional And Mechanical Role Of Splice Variant Of Mucin4 (Muc4/X) And Trefoil Factors In Pancreatic Cancer Pathogenesis, Rahat Jahan

Theses & Dissertations

Pancreatic Cancer (PC) is one of the vicious cancers as it ranks third in the race of leading cause of cancer-related death. Lack of early diagnostic marker, poor understanding of molecular mechanism of the disease and failure to conventional chemotherapy makes this disease dreadful.

Mucin 4 (MUC4), a high molecular weight glycoprotein is one of the top differentially expressed molecules in PC while not expressed in normal pancreas. Accumulating evidence from our lab suggested its tumorigenic role in PC by increasing cell proliferation, invasion, chemotherapy resistance, tumor growth, and metastasis. Previously, our lab and other has identified 24 different splice …

Precision Medicine In Pediatric Cancer: Current Applications And Future Prospects., Atif Ahmed, Divya S. Vundamati, Midhat S. Farooqi, Erin M. Guest

Manuscripts, Articles, Book Chapters and Other Papers

Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor's variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up, with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the …

Retrospective Review Of Oral Oncolytic Agent Use Within A Community Hospital, Alyssa Donadio, Moe Shwin, Maria Figueroa, Michelle Lamarque

All Publications

No abstract provided.

The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic

Electronic Thesis and Dissertation Repository

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations & Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

The Tumor Microenvironment Regulates Retinoblastoma Cell Survival, Zachary K. Goldsmith

Theses and Dissertations (ETD)

Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of …

Targeting The Colchicine Binding Site On Tubulin To Overcome Multidrug Resistance And Anticancer Efficacy Of Selective Survivin Inhibitors, Kinsle E. Arnst

Theses and Dissertations (ETD)

Tubulin inhibitors are widely used as chemotherapeutic agents, and their successis attributed to their ability to target microtubule dynamics and disrupt critical cellular functions including cell signaling, motility, intracellular trafficking, and mitosis. Interference with microtubule dynamics consequently disrupts mitotic progression and ultimately leads to apoptosis, validating microtubule dynamics as an excellent target for anticancer agents. While this class of drug has proven to be effective against many cancer types, the clinical efficacy of current tubulin inhibitors is often limited by the development of multidrug resistance. The most common form of resistance to these agents arises from the overexpression of drug …

Hepatocarcinoma With Tumor Thrombus Occupying The Right Atrium And Portal Vein In A Patient With Hereditary Hemochromatosis And Liver Cirrhosis, Olga Hilda Orasan, Andreea Maria Stefan, Laura Urian, Anca Mihailov, Ovidiu Fabian, Flaviu Muresan, Iulia Breaban, Sorina Cezara Secara, Simina Tarmure Sarlea, Vasile Negrean, Dorel Sampelean, Angela Cozma

Journal of Mind and Medical Sciences

We present the case of a 46-year old patient with Child-Pugh class C cirrhosis with MEDL-Score 16, and hepatocellular carcinoma invading the inferior vena cava and the right atrium. The etiology of cirrhosis is type 1 hereditary hemochromatosis with positive HFE C282Y/C282Y and H63D/H63D mutations. A systematic review of the literature was performed and only 30 cases of hepatocellular carcinoma with tumor thrombosis extending into the right atrium have been described. To our knowledge, this is the first case that evidences the presence in hereditary hemochromatosis of hepatocellular carcinoma with atypical invasion into the right atrium. Screening of patients with …

8th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan

Electronic Thesis and Dissertation Repository

The lung is among the deadliest sites of breast cancer metastasis. Previous work from our laboratory demonstrated that aggressive CD44-expressing breast cancer cells preferentially metastasize to the lung in vivo, and observed the presence of multiple CD44-interacting proteins in the lung including E-, L- and P-selectin. We hypothesized that lung-derived selectins promote breast cancer migration and/or growth via interactions with CD44. Using an ex vivo model of the soluble lung-microenvironment, we demonstrate that lung-derived selectins enhance in vitro migration but not proliferation of breast cancer cells. Co-immunoprecipitation experiments reveal that CD44 expressed by breast cancer cells in vitro interacts …

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …

Immunohistochemical Analysis Of Basigin And Axl Expression In Gliomas, Brittney N. Moore

Conspectus Borealis

No abstract provided.

Impact Of Feeding Tube Status On Health Outcomes For Individuals With Oropharyngeal Cancer, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Abstract

This study investigated differences in outcomes related to health, swallowing, and quality of life (QoL) for individuals with oropharyngeal squamous cell carcinoma (OPSCC) receiving either radiotherapy (RT) alone, or concomitant chemoradiotherapy (CRT). Differences were assessed based on whether patients received a feeding tube (FT group) or not (NFT group). Measures including the Functional Oral Intake Scale (FOIS), Performance Status Scale for Head and Neck Cancer (PSS-HN), M.D. Anderson Dysphagia Inventory (MDADI), and weight were collected for 126 individuals at baseline, and at 3, 6, and 12 months post-treatment. Data were analyzed to identify potential prognostic differences between the groups, …

Inhibition Of Ribosome Biogenesis Through Genetic And Chemical Approaches, Leonid Anikin

Graduate School of Biomedical Sciences Theses and Dissertations

In order to maintain the ability to generate proteins, proliferating cells must continuously generate ribosomes, designating up to 80% of their energy to ribosome biogenesis (RBG). RBG involves transcription of rDNA by RNA polymerases I (Pol I) and III (Pol III), expression of approximately 80 ribosomal proteins, and assembly of these components in a process referred to as ribosome maturation. During maturation, the Pol I transcribed 47S pre-rRNA undergoes a number of processing events, while simultaneously interacting with processing factors and ribosomal proteins that drive pre-ribosome assembly. Inhibition of RBG has become one of the pursued targets for cancer therapy …

Simvastatin Does Not Sensitize Ibc3 Her2+ Inflammatory Breast Cancer Brain Metastases To Whole Brain Irradiation In An Immunocompromised Mouse Model, Swaminathan Kumar

Dissertations & Theses (Open Access)

Retrospective data analysis suggests that inflammatory breast cancer (IBC) patients who take statins have better locoregional control after radiotherapy than those who do not [23]. Our lab has previously demonstrated that simvastatin radiosensitizes IBC cells in vitro [23], and brain metastases have strong expression of cholesterol-regulation genes compared to lung metastases in vivo [unpublished]. Delaying whole-brain irradiation (WBI) beyond 21 days is insufficient to reduce the incidence of brain metastases (developed by injecting IBC3 cells through the tail vein) in our mouse model because even high rates of cell killing leave substantial cell volume in established metastases [unpublished].

With the …

Aminoflavone Inhibits Α6-Integrin And Growth Of Tamoxifen Resistant Breast Cancer, Petreena S. Campbell

Loma Linda University Electronic Theses, Dissertations & Projects

Approximately 40% of estrogen receptor positive (ER+) breast cancer patients develop resistance to standard of care agent tamoxifen, while ER negative (ER-) breast cancer patients are intrinsically resistant to tamoxifen. Resistance often promotes metastasis, recurrence and death. Tumor-initiating cells (TICs) represent key contributors to resistance and adhesion protein α6-integrin is a putative TIC biomarker. Investigational agent Aminoflavone (AF) demonstrates efficacy against breast cancer cells irrespective of ER status. Interestingly, we found tamoxifen resistant (TamR) cells and tumors exhibited elevated α6-integrin expression in comparison to their tamoxifen sensitive counterparts. AF effectively disrupted mammospheres enriched for TICs and reduced α6-integrin levels in …

Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross

Loma Linda University Electronic Theses, Dissertations & Projects

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …

Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit

Electronic Theses and Dissertations

Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, …

Racial Disparity Among Women Diagnosed With Invasive Breast Cancer In A Large Integrated Health System, Maharaj Singh, Santhi D. Konduri, George C. Bobustuc, Amin B. Kassam, Richard A. Rovin

Journal of Patient-Centered Research and Reviews

Purpose: Reasons for the well-described disparity in outcomes between African American (AA) and non-Hispanic white (NHW) women with invasive breast cancer are unclear, making it difficult to identify solutions. This study examined the effects of demographics, biomarkers, tumor characteristics, cancer stage, morphology, and treatment variables on overall and cancer-free survival in these patient populations.

Methods: We retrospectively reviewed data for 6231 patients diagnosed with invasive breast cancer throughout an integrated health system from January 2006 through March 2015. Included for analysis were 5023 NHW and 413 AA women. All category and continuous variables in the study were described in the …

Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes

LSU Doctoral Dissertations

Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …

Tgf-Β Sustains Tumor Progression Through Biochemical And Mechanical Signal Transduction., Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development is critical for designing therapeutics that …

Economic Evaluation Of Patient Navigation Programs In Colorectal Cancer Care, A Systematic Review., Chloé Gervès-Pinquié, Anne Girault, Serena Phillips, Sarah Raskin, Mandi Pratt-Chapman

Pediatrics Faculty Publications

Patient navigation has expanded as a promising approach to improve cancer care coordination and patient adherence. This paper addresses the need to identify the evidence on the economic impact of patient navigation in colorectal cancer, following the Health Economic Evaluation Publication Guidelines. Articles indexed in Medline, Cochrane, CINAHL, and Web of Science between January 2000 and March 2017 were analyzed. We conducted a systematic review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality assessment of the included studies was based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Inclusion criteria …

The Role Of Glucocorticoid Signaling In Prostate Cancer Health Disparities, Leanne W. Burnham

Loma Linda University Electronic Theses, Dissertations & Projects

African-American men are more likely to develop aggressive prostate cancer (PCa) and die from the disease than other ethnic groups. Glucocorticoid signaling is a contributing biological factor to worse PCa prognosis, and is emerging as a key driver of PCa progression in the absence of androgens. The mechanism involves glucocorticoids binding to glucocorticoid receptor (GR) and bypassing the androgen receptor (AR) signaling pathway to activate AR-target genes that promote tumor aggressiveness and therapy-resistance. This is problematic as African-American men have hypersensitive GR signaling and chronically-elevated levels of glucocorticoids linked to cumulative stressful life events. To explore the role of glucocorticoid …

Myeloid Sarcoma: A Rare Cause Of Small Bowel Obstruction, Jonathan Sedeyn Do, Phd, Karlbuto Alexandre, Alan J. Sheinbaum Do, Adeshola Fakulujo Md, Facs

Rowan-Virtua Research Day

Myeloid sarcoma is a rare and aggressive tumor of myelogenous origin that uncommonly presents in the small bowel. Here we describe the case of a 29 year old male with a two week history of worsening abdominal pain associated with nausea and bilious vomiting. The patient displayed tenderness in the epigastric and periumbilical region with grossly normal lab values. On CT he was found to have a small bowel obstruction with a transition point in the pelvis. Exploration revealed a small bowel mass located approximately 12 cm from the ileocecal valve. Pathological analysis showed large malignant cells with a high …

Metastatic Breast Cancer Presenting As Painless Jaundice, Daniel S. Wilen Do, Donald J. Mcmahon Do, Brian J. Blair Do, Joanne Kaiser-Smith Do, Darshan B. Roy Md

Rowan-Virtua Research Day

Breast cancer is the most commonly diagnosed cancer in women in the United States. Treatment options are wide-­‐ ranging based on a multitude of factors, including extent of disease and receptor positivity. Following treatment, a relapse-­‐free interval ≥ 2 years carries a more favorable prognosis.

We present a case involving a female with history of breast cancer and relapse-­free interval of 15 years who unfortunately presented with metastatic disease involving the liver, bone, and lymph nodes.

A Case Of Synchronous Colorectal Carcinoma Manifested As Three Separate Colon Masses, Alyssa Imperatore Do, Linda Szczurek Do, Facos, Alan Shienbaum Do

Rowan-Virtua Research Day

Colorectal cancer is the second leading cause of cancer-related deaths in the United States amongst cancers that affect both genders. Synchronous colorectal cancer is greater than one primary lesion detected on initial presentation and occurs about 5% of the time.

This is a 78 year-old female with past medical history of left-sided breast cancer treated with neoadjuvant chemotherapy who presented with symptomatic anemia found to have a hemoglobin of five and positive fecal occult blood test. Patient was transfused and taken for EGD/colonoscopy, which showed three polypoid rectal lesions and three separate colon masses. Preliminary pathology showed high grade dysplasia …

Gist- An Unusual Case Of Gi Bleeding, Lucy Joo Do, Justin Derosa Do, Drew Chiesa Do, Darshan Roy Md

Rowan-Virtua Research Day

This is a unique case of a female who was diagnosed and treated with a GIST (gastrointestinal stromal cell tumor) of the stomach.The purpose is to deliver awareness and education to clinicians of this rare malignancy by emphasizing its presentation and characteristics.

A Case Of Signet Ring Cell Colon Carcinoma Initially Presenting As Acute Diverticulitis, Justin Derosa Do, Jonathan Foster Do, Drew Chiesa Do, Darshan Roy Md

Rowan-Virtua Research Day

This is a unique case of a female with an acute bout of diverticulitis who six weeks later on follow up colonoscopy, was found to have signet ring cell colon carcinoma. The purpose is to deliver awareness of this rare type of colon malignancy, emphasize the continued need for screening colonoscopy, and to provide the reader with a distinct and thought provoking spin on the conventional diagnosis of diverticulitis.